Betaines are neutral chemical compounds with a positively charged cationic functional group, usually a quaternary ammonium or phosphonium group, and a negatively charged functional group, usually as a carboxylate group. A betaine is thus a zwitterion. Historically, the term “betaine” referred only to the specific compound N,N,N-trimethylglycine.
Many betaines are vitamins, pharmaceuticals or precursors thereof. They are used as food additives, diet components or pharmaceuticals. An important betaine is carnitine (vitamin Bt; 3-hydroxy-4-(trimethylammonio)butanoate). Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. Carnitine exists in two stereoisomers. The biologically active form is L-carnitine (levocarnitine, LC), whilst its enantiomer, D-carnitine, is biologically inactive. L-carnitine is an endogenous compound, which plays a key metabolic role, transporting long chain fatty acids into the mitochondria for energetic oxidation. Supplementation with acetyl-L-carnitine (ALC) has been shown to increase overall regional cerebral metabolism in rodents. Carnitine and its esters also have non-metabolic roles in brain function as neuroprotectants, antioxidants and modulators of neurotransmission.
Betaines, such as carnitine, are usually produced by organic synthesis at an industrial scale. Typically, solutions of betaines in solvents, for example in aqueous solution or in ethanol, are obtained. The solutions and solid products are subjected to purification steps for obtaining the betaine at high purity, thereby removing salts, solvent, residual starting products, side products and the like. Common purification steps comprise crystallization, recrystallization, washing of crystallized products, distillation, filtration and salt removal by ion exchange chromatography. As a result, highly concentrated betaines are obtained in solid form.
Typically, solid betaines, such as carnitine, are colorless and solutions thereof are likewise colorless and transparent. However, when such betaines are produced by organic synthesis, and even when purified thereafter, often colorized products are obtained. For example, carnitine produced by organic synthesis usually has a brown or yellow coloration. The reason for the coloration is not precisely known.
Methods in the art for producing carnitine usually comprise a decoloration step, wherein a solution comprising the carnitine product is contacted with activated carbon. Activated carbon (active carbon, activated charcoal, activated coal) is a non-polar adsorbent capable of binding large amounts of non-polar substances due to its high internal surface. After sufficient incubation time, a colorless solution is obtained, whilst compounds causing the coloration are absorbed by the carbon. Betaines are not bound to the activated carbon and thus decolorized. For example, the problem of colorized carnitine products and decoloration with activated carbon are disclosed in WO2007/003425 A2 (page 2, lines 14 to 22), US 2009/0325246 (section [0100]) or EP 2 360 141 A1 (section [0039]).
In the state of the art, ion exchange chromatography is applied for desalting aqueous solutions of compositions comprising L-carnitine and converting L-carnitine salts into the inner salt. CN101337902 A discloses a method for purifying L-carnitine from aqueous solutions, in which pre-desalting steps are carried out with electroosmosis and an anion exchange material, where after a decoloring treatment is carried out with activated carbon.
CN101875616 discloses another method for producing L-carnitine, wherein a desalting step is carried out with an ion exchange material.
Decolorization of betaine solutions with activated carbon has certain drawbacks. At first, activated carbon is relatively costly, especially when used in a large-scale industrial process. Columns, which are packed with activated carbon, cannot be recycled efficiently. The efficiency of decoloration is not always sufficient and relatively large amounts of activated carbon are required for quantitative decoloration. Trace amounts of carbon may remain in the product and may interfere with subsequent reactions or uses, for example when subsequent reactions are carried out with sensitive catalysts.
Moreover, decolorization with activated carbon, although efficient in aqueous solutions, is not efficient in some organic solvents, such as ethanol. However, synthesis of betaines in ethanol is an important industrial process. Thus there is a need for efficient decoloring of betaines directly in such solutions in organic solvents.
WO96/15274 relates to methods for decolorizing aqueous solutions in the sugar industry, which comprise high amounts of sugars and may comprise additional N,N,N-trimethylammonioacetat (“betaine”). The inventors suggest decoloration of the sugar solutions with polyaluminum chlorides.
DE 1 136 711 relates to methods for extracting N,N,N-trimethylammonioacetat (“betaine”) from natural products, such as sugar rich juices and molasses. The process is carried out with aqueous sugar-rich solutions and requires several consecutive ion exchange treatment steps with cation and anion exchange resins.
DE 196 34 640 A1 relates to methods for desalting aqueous solutions comprising precursors for the production of L-carnitine. The method comprises at least electrodialysis and cation exchange chromatography. The method does not relate to decoloration of the solutions. Further, it is relatively complicated and requires long treatment times of about 8 to 12 days.
It would be desirable to provide a process for decoloring betaines and betaine solutions, especially carnitine and carnitine solutions, which overcome the above mentioned problems. Specifically, it would be desirable to provide a process which does not require a decoloration treatment with activated carbon, and which is also efficient in organic solvents.